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Prioritization of potential causative genes for schizophrenia in placenta

Author

Listed:
  • Gianluca Ursini

    (Johns Hopkins University Medical Campus
    Johns Hopkins University School of Medicine)

  • Pasquale Di Carlo

    (Johns Hopkins University Medical Campus
    Neuroscience and Sense Organs, University of Bari Aldo Moro)

  • Sreya Mukherjee

    (Johns Hopkins University Medical Campus)

  • Qiang Chen

    (Johns Hopkins University Medical Campus)

  • Shizhong Han

    (Johns Hopkins University Medical Campus)

  • Jiyoung Kim

    (Johns Hopkins University Medical Campus)

  • Maya Deyssenroth

    (Icahn School of Public Health at Mount Sinai)

  • Carmen J. Marsit

    (Rollins School of Public Health, Emory University)

  • Jia Chen

    (Icahn School of Public Health at Mount Sinai)

  • Ke Hao

    (Icahn School of Medicine at Mount Sinai)

  • Giovanna Punzi

    (Johns Hopkins University Medical Campus
    Johns Hopkins University School of Medicine)

  • Daniel R. Weinberger

    (Johns Hopkins University Medical Campus
    Johns Hopkins University School of Medicine
    Johns Hopkins School of Medicine
    Johns Hopkins School of Medicine)

Abstract

Our earlier work has shown that genomic risk for schizophrenia converges with early life complications in affecting risk for the disorder and sex-biased neurodevelopmental trajectories. Here, we identify specific genes and potential mechanisms that, in placenta, may mediate such outcomes. We performed TWAS in healthy term placentae (N = 147) to derive candidate placental causal genes that we confirmed with SMR; to search for placenta and schizophrenia-specific associations, we performed an analogous analysis in fetal brain (N = 166) and additional placenta TWAS for other disorders/traits. The analyses in the whole sample and stratifying by sex ultimately highlight 139 placenta and schizophrenia-specific risk genes, many being sex-biased; the candidate molecular mechanisms converge on the nutrient-sensing capabilities of placenta and trophoblast invasiveness. These genes also implicate the Coronavirus-pathogenesis pathway and showed increased expression in placentae from a small sample of SARS-CoV-2-positive pregnancies. Investigating placental risk genes for schizophrenia and candidate mechanisms may lead to opportunities for prevention that would not be suggested by study of the brain alone.

Suggested Citation

  • Gianluca Ursini & Pasquale Di Carlo & Sreya Mukherjee & Qiang Chen & Shizhong Han & Jiyoung Kim & Maya Deyssenroth & Carmen J. Marsit & Jia Chen & Ke Hao & Giovanna Punzi & Daniel R. Weinberger, 2023. "Prioritization of potential causative genes for schizophrenia in placenta," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-38140-1
    DOI: 10.1038/s41467-023-38140-1
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